As part of the search for naturally derived α-glucosidase inhibitors, the chemical components isolated from safflower seed (Carthamus tinctorius L.) were evaluated. The compounds active as α-glucosidase inhibitors were serotonin derivatives (e.g. N-p-coumaroyl serotonin (1) and N-feruloyl serotonin (2)). These compounds showed a potent inhibitory activity, the 50% inhibitory concentration (IC(50) ) values were calculated as 47.2 µm (1) and 99.8 µm (2) while that of the reference drugs acarbose and 1-deoxynojirimycin were evaluated as 907.5 µm and 278.0 µm, respectively. Regarding the structure of the serotonin derivative, the existence of the hydroxyl group at 5-position in the serotonin moiety and the linkage of cinnamic acid and serotonin are essential for α-glucosidase inhibitory activities. These results are helpful for the proper use of safflower seed as traditional medicine for the treatment of diabetes, moreover, it could serve to develop medicinal preparations as supplements and functional foods for diabetes. In particular, the serotonin compounds could be used as a lead compound for a new potential α-glucosidase inhibitor derived from the plant.